In sensory neurons of the eye and inner ear the neurotransmitter, glutamate, is released at active zones in a graded and continuous manner. In these neurons specialized structures have evolved, known as synaptic ribbons. Synaptic ribbons are osmiophilic proteinaceous structures that tether synaptic vesicles near active zones. Because of their morphology, location within the cells and the cell types where they are found, these organelles are undoubtedly important for the continuous release of glutamate; how ribbons aid in this task, however, remains unclear. The focus of this grant is to study the role of synaptic ribbons in sensory synaptic transmission, with the long term goal to resolve the temporal sequence of events that are involved in the release of neurotransmitter from these important cells. Specific Aim 1 is to look at how vesicles attach to the ribbon and to plasma membrane at sites away from the synaptic ribbon. Specific Aim 2 will look at the properties of synaptic release. Specific Aim 3 explores the plasticity of the synaptic ribbons. Understanding ribbon function may provide clues to help understand diseases that specifically affect vision and hearing. In addition, the fundamental understanding of presynaptic processes in these specialized neurons will have broader implications for neuronal communication in general and thus, may contribute to our understanding of various aspects of mental health and neurological disorders. PUBLIC HEALTH RELEVANCE: Information in the nervous system is transmitted between nerve cells at the synapse, where an electrical impulse in the "presynaptic" nerve cell causes the release of neurotransmitter from small membrane bound structures, known as synaptic vesicles. In sensory neurons of the eye and inner ear the neurotransmitter, glutamate, is released from synaptic vesicles in a graded and continuous manner and deficiencies in this process may underlie hereditary forms of blindness and deafness. This proposal studies the tonic release of neurotransmitter from one such specialized neuron in the retina. [unreadable] [unreadable] [unreadable]